With the advent of rapid advances in surgical techniques and the development of new biocompatible materials for prosthetic implants, researchers have also focused their attention on development of new tissue/implant fixation techniques. One facet of such research has been the formulation of surgical adhesives that can be used as a substitute for, or in combination with, standard mechanical fixation techniques. Recently biocompatible adhesives for surgical use have been proposed based, at least in part, on what has been learned about natural bioadhesives, for example, the proteinaceous compositions produced by barnacles that allow that species to attach themselves with seemingly permanent fixation to a wide variety of underwater structures. Much has been learned about the "chemistry" of such natural adhesives, and efforts are being made to harness such chemistry for production of glues and adhesives for use in surgical applications.
The present invention is based on the use of "chemistry", albeit different from the chemistry of marine-derived natural adhesives, to optimize adhesive function under physiological conditions. More particularly, the invention is based on the reactivity of certain polymer-associated functional groups with tissue-associated functional groups. The adhesive composition reacts with and forms covalent bonds with tissue in vivo. The functional groups on the adhesive polymer components of the present composition are selected such that upon reaction with functional groups on the molecular components of tissue, there is propagated a second reactive functional group that can in turn react intramolecularly or intermolecularly with at least one other functional group on the adhesive polymer to effect covalent crosslinking and "setting" of the adhesive in vivo.
Thus in accordance with one embodiment of the invention there is provided a tissue-reactive adhesive composition comprising a biocompatible polymer substituted with at least one tissue reactive functional group.
In another embodiment the substituted biocompatible polymer is combined with a monomer or oligomer having at least a tissue reactive substituent and a thiol-reactive substituent to form the tissue-adhesive composition.
In another embodiment of this invention the tissue-adhesive composition further comprises effective amounts of one or more biologically active components to form a self-adhesive implant capable of providing sustained release of the biologically active component in vivo.
In another embodiment of this invention the tissue-reactive adhesive composition can be utilized alone or in combination with mechanical fixation techniques as a surgical glue for adjoining tissue surfaces or for fixation of prosthetic implants.